This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The relationship between a given protein's structure and its molecular function can be quite complex, yet recently some of the fundamentals have been elucidated through the study of enzyme superfamilies. The Resource for Biocomputing, Visualization, and Informatics (RBVI) and the Babbitt lab are developing the SFLD (Structure-Function Linkage Database) database to leverage this information in a manner which will allow users to predict and engineer enzyme function. The SFLD is now a web-accessible database hosted by the RBVI. Currently supported are methods allowing users to search the database with a protein sequence, keyword (matching enzyme or reaction name), or with a reaction, substrate, product, or partial reaction as described by a SMILES string. Easy (i.e. single click) methods for users to visualize protein structures within the SFLD using Chimera are available. A web interface allowing curators of the SFLD to input and update information has recently be implemented, and is used by all current curators. A paper describing aspects of the SFLD was presented at the Pacific Symposium for Biocomputing in January 2005. The visibility of the SFLD continues to increase, aided by a very well-received, high-profile publication (Biochemistry, 2006 45(8):2545-55) and mutiple presentations at meetings. This increased visibility has drawn interest from multiple researchers outside UCSF who would like to use the SFLD as a data management tool for their own superfamily information. One focus of future work involves the development of tools and training procedures to aid these researchers in utilizing the SFLD for their own research purposes. The SFLD is available to the public at http://sfld.rbvi.ucsf.edu.